One major problem in RNA sequence analysis lies in the lack of a truly general method which permits the preparation of sets of specific oligonucleotides of intermediate length which could be independently isolated, their structures determined, and their overlapping segments used to permit reconstruction of the sequence of the original macromolecule. Partial ribonuclease digestion has been used thus far, but relies on native secondary or tertiary structure in the RNA studied. Antibodies can be induced which are able to recognize a specific nucleotide or base sequence. It is proposed that nucleotide sequence specific antibodies be induced with appropriate oligonucleotides coupled to a synthetic polypeptide or protein carrier. The antibodies would be isolated by affinity chromatography and freed of contaminating ribonuclease activity, and the interactions of antibodies with mononucleotides, oligonucleotides, and synthetic and natural polynucleotides would be characterized. One type of sequence specific antibody would then be complexed with specific (recognized) sequences in viral RNA, the complex treated with a specific nuclease to cleave the RNA at regions unprotected by antibody, and the resulting oligonucleotides isolated and characterized. A second type of antibody could then be used to protect different segments of the RNA, and nuclease used to generate a second set of oligonucleotides. If necessary further oligomers could be generated with other protective antibodies present in the hydrolysis mixture. Initial experiments would employ viral RNA labeled in the 3'-terminal nucleotide and terminal fragments characterized as a test of the methods.